Friedreich’s Ataxia: An overview of current trials being offered through USF

19th Nov 2015 Friedreich's Ataxia

Friedreich’s ataxia was first recognized by Nikolaus Friedreich over 150 years ago.  For nearly two decades, researchers have been focused on identifying the underlying cause of FA and treatments to reduce symptoms and cure this disease.

There are a number of investigational drugs and treatments which are currently in clinical trials. Here locally in Tampa, The University of South Florida (USF) Ataxia Research Center is leading the way in testing and developing new treatments.  USF is one of 10 sites in the international Friedriech’s Ataxia Research Alliance (FARA) collaborative clinical research alliance.  Some novel approaches are being used to increase frataxin production, reduce mitochondrial damage while improving overall mitochondrial function, reducing oxidative stress, and delivering gene therapies.

Here is an overview of the current FA related clinical trials being conducted through the USF Ataxia Research Center:

Randomized, Double-blind Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of RT001 in Patients with FA.  RT001 is a compound developed by a Retrotope (clinical-stage pharmaceutical company).  The patented drug is a stabilized fatty-acid that is aimed at shutting down degradation of cellular membranes that are believed to be associated with neurodegenerative diseases and the aging process.

Phase I, Randomized, Double Blind, Placebo-controlled, Multicenter, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Oral VP 20629 in Adult Subjects with FA.   This study sponsored by biopharmaceutical company, Shire, is focusing on a low molecular weight drug (indole-3-propionic acid). This is considered a powerful antioxidant to help alleviate free radical damage from iron buildup from within the cells.

Phase 2 Study of the Safety, Efficacy, and Pharmacodynamics of RTA 408 in the Treatment of Friedreich’s Ataxia (MOXl1).  RTA 408 compound, developed by Reata Pharmaceuticals is believed to activate the Nuclear Factor 2 pathways which regulates the expression of antioxidant proteins. This study will be conducted in two parts. The first is to test the study drug at various dose levels. The second part of the trial will be focus on two specific dose levels of RTA 408 as compared to a placebo.


Randomized, Multicenter, Double-Blind, Placebo-Controlled, Efficacy, Safety, and Pharmacokinetic Study of ACTIMMUNE in Children and Young Adults with FA.  Interferon gamma-1b is a biologically manufactured protein that is similar to the one produce by the body’s own immune system. This drug is already approved in the U.S.  for two rare diseases and has received fast track approval by the FDA in the treatment of FA. Interferon gamma plays a role in the regulation of iron availability.  From previous trials, this drug has shown the potential to increase the production of frataxin protein.

Drug-Resistant Head Lice

21st Oct 2015 Medical News

Every year, millions of school aged children get head lice. Typically this has been more of a nuisance problem than a serious illness.

Lice are considered ectoparasites that live exclusively on the human scalp and feed off of human blood. Head lice are wingless insects that spread by close contact between people such as with sharing headwear, combs, brushes, towels and clothes. Head lice live approximately 28 – 30 days and multiply quickly. Female lice can lay as many as 90 eggs and within 15-20 days mature into adult lice. Itching is the number one symptom of lice infestation and may take up to several weeks before this starts. Head lice do not transmit communicable diseases.

It is estimated that as many as 12 million children, most commonly pre and elementary school aged, are treated in the U.S. annually for this disease. Treatment is usually by medication containing the active ingredient, permethrin.

Unfortunately, treatment of head lice is becoming a complex issue. A research team from Southern Illinois University collected lice samples from individuals in over 30 states. Of the samples collected, 104 out of 109 lice populations had gene mutations leading to treatment resistence. To date, more than 25 states have reported resistant head lice. It is believed that resistance to standard medications developed just as antibiotic resistance has. The overuse and misuse of permethrin in this case has led to the development of super lice which make them immune to standard treatments.

Fortunately, several pharmaceutical companies have developed other products that are effective against head lice. Many of these require a doctor’s prescription. The use of home remedies including olive oil, coconut oil, clove oil, and essential oils such as tea tree have also been reported treatments for head lice. While many of these are considered “natural”, the safety and efficacy is unknown.

Keys to treating head lice include using an effective treatment (prescription medication, OTC medication, or natural home remedy), combining the hair carefully to remove nits, vacuuming the home and washing suspected clothing and linens, and daily head checks until infestation is gone. Management of head lice is easier the earlier infestation is identified.



Yook KS et al. In Vitro and In Vivo Evaluation of Infestation Deterrents Against Lice. J. Med Entomology. 2015 2015: 52(5):970-978.

Where do we stand with preventing Breast Cancer?

14th Oct 2015 Diseases, Medical News

The month of October is about raising awareness of breast cancer and advocating for early detection. Approximately 1 in 8 women born in the U.S. are at risk for developing this disease. The big question is where do we stand with preventative efforts?

Statistics have shown that the incidence of breast cancer has increased by more than 20 percent worldwide since 2008. We still do not have a cure for breast cancer, but there is strong evidence to suggest that lifestyle and diet may play a large part in the disease process. A study published in the Journal of the American Medical Association (JAMA) in September 2015, found that those women who consumed a Mediterranean diet, which is rich in olive oil, had a significantly decreased risk of breast cancer over those who consumed a low fat diet. This study included more than 4000 women between the ages of 60 and 80 years old. What remains unclear is if the reduction in breast cancer was due to the olive oil alone or if the effect was from the overall diet.

In another study, published in the International Journal of Cancer, a link between metabolic syndrome and increased risk of breast cancer was suggested. Metabolic syndrome may include high glucose levels, high triglycerides, high blood pressure, low HDL (“good cholesterol”), and obesity. All of these factors are strongly tied to diet and lifestyle.

In the latest reported findings, taken from a study that is currently in progress, heavy doses of chemotherapy are no longer warranted in the early treatment of the most common type of breast cancer. This study includes more than 10000 women who have been previously diagnosed with breast cancer. Of those in the low risk group, 99% of survivors had no relapses within 5 years of diagnosis, while 94% were free of any invasive breast cancer. A U.S. company, Genomic Health, claims that their new genomic test can decide whether chemotherapy is warranted for a specific case of breast cancer and whether or not reoccurrence is likely to occur.

Based on current practice and research, it is believed that the risk of breast cancer can be lowered with 5 simple lifestyle changes:

  1.  Healthy diet that is low in processed foods and sugars
  2.  Avoidance of smoking
  3.  Maintaining a healthy weight
  4.  Avoidance of alcohol
  5.  Daily exercise




Toledo E et al. Mediterranean Diet and Invasive Breast Cancer Risk Among Women at High Cardiovascular Risk in the PREDIMED Trial: A Randomized Clinical Trial. JAMA. 2015 Sept 14:1-9.

National Breast Cancer Foundation, Inc. –

Influenza 101: This year’s flu and the next big concern

25th Sep 2015 Diseases, Viruses

It has been widely reported that this year’s flu vaccine is very ineffective. In fact, the CDC has now reported the vaccine effectiveness to be a dismal 18%. The reason for this is that the main virus that has been circulating, H3N2, is not included in this year’s vaccine. A universal vaccine is currently in clinical trials, but its effectiveness and release are currently unknown.

In review, there are three types of influenza or “flu” that affect humans (Type A, B, C). As we all know, the flu can cause symptoms that range from mild to severe including fever, sore throat, muscle pains, coughing, headaches, nausea, vomiting and lethargy. Type A influenza has been known to be associated with the worst outbreaks and cause the most severe disease. Wild birds are the natural host for this type of flu. While similar to the influenza virus, the avian form of influenza is from a different subspecies. All influenza that has occurred in birds is from the Type A subspecies. The avian flu has historically been lethal and has caused many deaths worldwide.

The ‘H’ in H3N2 refers to hemagglutin which is a glycoprotein that binds the virus to the host cell. ‘N’ refers to neuraminidase which is an enzyme found on the surface of the influenza virus that enables the virus to be released from the host cell. The numbers that accompany H and N refer to subtypes of the virus.

There have been several strains that have been associated with pandemics. H1N1, H2N2 and H3N2 subtypes were avian based. Newer subtypes of H1N1 include the swine flu.

In 2013, the emergence of H7N9 in China has raised concern for another worldwide pandemic. H7N9 is an avian based subtype but it has been reported that transmission from person to person may have occurred. There is a much larger mortality rate associated with H7N9 than with other subtypes. In fact, nearly one third of those infected during a 2013 outbreak died from complications associated with the disease. Some infectious disease specialists and researchers have laid claim that N7N9 could cause a worldwide pandemic, similar to the last one seen in 1918 which caused over 100 million deaths.

The first case of H7N9 in North America was reported earlier this year. A Canadian citizen tested positive for the disease upon returning home from Hong Kong in late January.

The underlying source for H7N9 appears to be from infected chickens that has spread rapidly among several provinces in China. There has been very limited reports of human to human transmission. The World Health Organization (WHO) is calling H7N9 one of the most lethal viruses seen. A vaccine is currently in clinical trials.


Cardiomyopathy in Friedreich’s Ataxia

18th Sep 2015 Diseases, Friedreich's Ataxia

A recently published study conducted through the New York Veterans Affairs Medical Center in Albany, looked at the association between Friedreich’s Ataxia (FA) and cardiomyopathy. While FA is known as a neurological disease, the most common cause of death in FA patients is cardiomyopathy. By definition, cardiomyopathy is a disease in which the myocardium becomes weakened or stretched resulting in decreased ability to pump blood to the rest of the body. As this progresses, arrhythmias and heart failure may result.

The study focused on 28 autopsy heart tissue samples from patients with FA. Additionally, 10 tissue samples were taken from healthy controls. Multiple measurements were made including X-ray fluorescence (XRF) of iron and zinc within the ventricle walls and interventricular septum, tissue frataxin, iron histochemistry, inductively-coupled plasma optical emission spectrometry (ICP-OES), and immunofluorescence of inflammatory markers hepcidin and CD68. Prior studies have focused on abnormalities related to left ventricular hypertrophy, dysfunction, and electrical abnormalities.

The tissue samples from hearts from FA patients showed evidence of hypertrophy and thickened walls. Muscle cells, known as cardiomyocytes were identified to be considerably larger in the control hearts. Additionally, the cardiomyocytes were surrounded by a layer of endomysium (fibrous connective tissue).

Further analysis of the tissue samples revealed a significant reduction in cardiac frataxin levels and higher levels of iron within the left ventricular wall and septum in FA patients. Furthermore, an abnormal number of CD68 reactive inflammatory cells was found in the hearts of FA patients. Cytosolic ferritin sequesters and stores iron to protect against free radical damage while hepcidin is a protein that plays a major role in iron regulation. Both of these markers were elevated in FA. The results of this study point have lead the researchers to believe that a strong iron expression seen in the cardiomyocytes might be a unique finding for cardiomyopathy in FA hearts. Since frataxin levels were low, the restoration of this mitochondrial protein and targeted anti-inflammatory therapy may be beneficial for those with FA.

The study was funded by the Friedrich’s Ataxia Research Alliance (FARA), National Ataxia Foundation, and the National Institutes of Health


Koeppen AH, Ramirez RL, Becker AB, Bjork ST et al. The Pathogenesis of Cardiomyopathy in Friedreich Ataxia. PloS One. 2015 Mar 4;10(3).

Alboliras ET, Shub C, Gomez MR, Edwards WD. Spectrum of Cardiac Involvement in Friedreich’s Ataxia: Clinical electrocardiographic and echocardiographic observations. American Journal of Cardiology. 1986 Sept 58(6): 518-524.

Predictors of disability among military personnel following a traumatic blast concussion

10th Sep 2015 Medical News

It is no surprise that military personnel who suffer a blast related brain injury are likely to experience post-traumatic stress disorder (PTSD) and depression. A recently published study out of the University of Washington in St. Louis has shown that when these early symptoms, which include anxiety, depression, flashbacks, and PTSD, occur within one week of the injury, they are a better predictor of long term disability than the results of common tests such as memory, thinking, and balance.

The prospective, observational study enrolled 38 U.S. military members who sustained a concussive traumatic brain injury. They were compared with 34 controls. All subjects who suffered injury were evaluated within 7 days at two sites in Afghanistan. The subjects were also re-evaluated again between 6 and 12 months post injury in the U.S. Service member’s ages ranged from 19 to 44 years old. Mental health was evaluated using a standardized military post-traumatic stress disorder questionnaire. Depressive symptoms and post-traumatic stress symptoms were elevated during the initial assessments while cognitive function was worse in subjects with a traumatic concussive injury. After the 6 – 12 month assessments, 63% of the subjects had moderate overall disability versus 20% in the control group. Moderate disability in this case is defined by inability to work in the same capacity as prior to injury, are unable to engage in normal social or leisure activities, and/or have disrupted relationships secondary to mental health disturbances.

It was believed that traditional measures including memory, attention, balance, and coordination would be the best predictors of long term disability. In this study these measures were not correlated with outcomes, but rather the psychological symptoms that were better predictors. It is unknown whether the psychological symptoms result from the brain injury, from stress related to war, or from other combined factors.

Having the knowledge that symptoms of PTSD and depression start much sooner than suspected in some cases, psychological evaluations should begin earlier and allow for earlier targeted care. The long term effect of this is unknown, but may offer the best chance to improve the quality of life. Researchers from the study also are planning to apply these findings in future studies looking at concussive brain injuries in the civilian world.

This study was conducted by investigators at the University of Washington in St. Louis and The U.S. Naval Medical Center in Portsmouth, Virginia.


MacDonald CL, Adam OR, Johnson AM, Nelson EC, Werner NJ, Rivet DJ, Brody DL. Acute post-traumatic stress symptoms and age predict outcome in military blast concussion. Brain. 2015 Mar 4.

Sequencing of common antibiotics may prevent drug resistant bacteria

04th Sep 2015 Diseases

Drug-resistant bacteria has become widespread. The World Health Organization (WHO) in 2014 made a plea for nations to monitor antibiotic resistance as there are serious public health consequences that can beginning to occur. A global survey showed alarmingly high rates of drug-resistant E-Coli and other bacteria that are capable of causing serious infections.

A recent study published by an international team based out of the University of Exeter in the UK has shown that alternating common antibiotics may prevent drug resistance. For many years, researchers have focused on using a combination of antibiotics as ‘cocktails’ with the thinking that a synergistic combination may be one answer to this growing problem.

In this recent study, the investigators used erythromycin and doxycycline to treat a test-tube model of resistant E-Coli. The antibiotics were given individually, in combination, and then in sequence. When given in certain sequences, they found that the infection was cleared. In most cases, the antibiotics given individually or combined failed to work. The researchers believe that specific doses of antibiotics combined with a specific sequence can make the bacteria sensitive and reduce risk of resistance.

As this was an experimental model, further research is needed to look at different combinations of drugs, doses and sequences.

Only two new classes of antibiotics have been introduced in the last 30 years. There is an urgent need to develop new drugs and while at the same time minimizing the prescribing and over utilization of antibiotics. Recently, the CDC announced that a drug-resistant form of the bacteria Shigella has caused illness in over 240 people since May 2014. 90% of the samples tested were resistant to the antibiotic Cipro. With more than 2 million cases of antibiotic resistant infections in the U.S. annually, rapid development of technologies to identify and characterize resistant bacteria has become a priority.


Fuentes-Hernandez A., Plucain J., Gori F., et al. Using a sequential regimen to eliminate bacteria at sublethal antibiotic dosages. PLOS Biology. 2015 April 8;13 (4).

National Action Plan for Combating Antibiotic-Resistant Bacteria-

A Lesser Known Tick-borne Illness: The Powassan Virus

28th Aug 2015 Diseases

Tick-borne illness in Florida and the U.S. has been on the rise. Lyme disease, Rocky Mountain spotted fever, and Babesiosis are some of the most widely reported diseases that occur from tick bites. Many have never heard of the Powassan virus, but it has the potential to cause more morbidity and mortality than these other tick borne illnesses.

The Powassan virus is spread by being bitten by an infected tick. The disease is named for the town in Ontario, Canada where the virus killed a young boy in the 1950’s. While the disease is found in the same type of tick that hosts Lyme disease, the Powassan virus is significantly faster acting and in many cases is untreatable.

At present there are six known species of tick that host the Powassan virus and are typically found in Canada, Minnesota and the northeastern U.S.. Since the virus was first identified in 1958, 70 cases have been reported. In reality, this number may actually be greater as there are no specific tests available for the Powassan virus and many may mistake it for Lyme disease.

There are no medications to treat the Powassan virus. Unlike Lyme disease which can take a couple of days before infection sets in, ticks infected with the Powassan virus can inject the virus within a few hours. Symptoms can be similar to a form of encephalitis and generally begin to show within one to three weeks after being bitten by an infected tick. Fever, vomiting, confusion, weakness, and headache are common symptoms reported. In severe cases, swelling of the brain, pareis, seizures, aphasia and altered mental status may be seen. It has been reported that the mortality rate is approximately 10%, however many of those that survive have permanent neurological complaints.

Fortunately, the number of reported cases and deaths associated with the Powassan virus is much less that what is to be expected considering the number of ticks that are infected.

While this disease has been occurring primarily in Canada and the northeast U.S., it is possible to see cases develop in other areas where conditions support tick populations. These tend to be in wooded areas. The use of tick repellents, long sleeves and long pants is advised. The CDC also advises that immediate bathing and skin checks should be conducted immediately after being outside.


Center for Disease Control and Prevention.

Minnesota Department of Health.

TitleGlobal study of disease and disability

21st Aug 2015 Medical News

A very interesting and eye opening study was published this month in THE LANCET in regards to the burden of disease across the world. Collaborators involved in the study analyzed over 35,000 sources of information on injury and disease from 188 countries with populations greater than 50,000 people between 1990 and 2013. Three hundred and one acute diseases, chronic diseases and injuries were included. Additionally 2337 sequelae that results from one or more of the studied disorders was also reviewed. There were many interesting findings. First and foremost, only 1 in 20 people had no health problems in 2013. Over 2.3 billion people (approximately 1/3 of the population) were experiencing more than 5 health ailments!

When researchers looked at the leading causes of years spent in less than optimum health, low back pain, depression, iron-deficient anemia, neck pain, and age related hearing loss have remained on top for nearly 23 years. The study collaborator’s attributed aging as the primary source leading to increasing disease and injury rates.

The study methodology including a review of published systematic reviews, re-analysis of household survey, data taken from hospital discharges, and from other administrative databases. Case reports to the World Health Organization (WHO) were also utilized. Disease estimates were calculated using a Bayesian meta-regression method. Bayesian refers to a method in statistics that utilizes probabilities of events. This allowed for computation of incidence and prevalence statistics for each country and time period. Specific data analyzed showed that under the category of acute disease, upper respiratory illness, interstitial nephritis, urinary tract infection, Dengue, pancreatitis, intestinal obstruction, and unintentional suffocation had the highest rates of increasing incidence during the study period. Similarly, for chronic disease (present for greater than 3 months), oral disorders, neurologic disease, skin disorders, musculoskeletal disorders, neglected tropical diseases, gynecologic disorders, and vision loss had the highest age-standardized rates.

Of the key findings noted from the study, rates of disability are declining at a much slower rate than mortality rates.

The data from this enormous research study have shown that there are many large causes of disability, or less than optimal health, that are largely preventable but require a greater focus or rates will continue to climb.

The study was funded by the Bill and Melinda Gates Foundation. The study funder reportedly had no role in the study design, data collection, data analysis, or data reporting.

Are low levels of Vitamin D associated with the development of dementia?

14th Aug 2015 Diseases, Medical News

A research study from the University of Exeter, published in the Journal of Neurology found a strong relationship between the development of Alzheimer’s disease and other forms of dementia and low levels of Vitamin D. The study included over 1600 adults over 65 years old who participated in the U.S. Cardiovascular Health Study. Participants of the study had their blood samples collected at the start of the study and mental status was assessed nearly 6 years later. Adults who had moderate Vitamin D deficiency had a 53% increased risk of developing dementia of any kind and 69% risk of develop Alzheimer’s disease. For those who were found to be severely Vitamin D deficient, there was a 125% risk of developing dementia and 122% increased risk of developing Alzheimer’s disease.

For the purposes of this study, a Vitamin D level of less than 50 nmol/L appeared to be threshold at which the risk of Alzheimer’s disease and other forms of dementia increased. This study is the largest yet to identify this association.

What remains unknown is the true cause and effect of this. It is unknown if increasing levels of Vitamin D would actually lower the risk of Alzheimer’s or dementia. More than 5 million people in the U.S. are affected by Alzheimer’s disease as the most common form of dementia. Worldwide, it estimated than over 44 million suffer from some form of dementia and this number is expected to grow with an aging population.

The authors of the study concluded that further studies are needed to establish whether the consumption of certain foods or taking a Vitamin D supplement can delay or prevent the onset of Alzheimer’s and dementia. The main source of Vitamin D for many is exposure to sunlight. However, the aging process results in skin that is less efficient at converting sunlight in a usable form of Vitamin D. Therefore, further supplementation through diet may be necessary to achieve adequate levels.

A group from the University of Guelph in Ontario, Canada has recently developed a mobile tracking application (‘App’) to help calculate intake of Vitamin D from food sources and exposure to sunlight. Using this newer technology as a tool may help users identify if they are below levels of adequate Vitamin D intake and lead to healthier behaviors.

References: Littlejohns TJ, Henley WE, Lang IA, Annweiler C, Beauchet O, Chaves PH, Fried L, Kestenbaum BR, Kuller LH, Langa KM, Lopez OL, Kos K, Soni M, Llewellyn DJ. Vitamin D and the risk of dementia and Alzheimer disease. Neurology. 2014 Sep 2; 83(10):920-8.

Goodman S, Morrongiello B, Simpson JR, Meckling K. Vitamin D intake among young Canadian adults: validation of a mobile Vitamin D Calculator App. Journal of Nutrition Education and Behavior. 2015; 47(3): 242.