MedicalResearch.com: What is the background for this study?
How does RT001 differ from other treatments for neurodegenerative diseases?
Response: Lipid peroxidation in critical cell and mitochondrial membranes represents a common pathway of cell death in many neurodegenerative diseases, regardless of the initiating trigger of original damage, e.g. aberrant gene expression, misfolded proteins such as tau and amyloid, environmental insults, etc. This hypothesis was supported by work showing that stabilizing lipids (using virtually indistinguishable isotopic variants of the original dietary molecules) was able to mitigate disease-related cell dysfunction, and reverse disease in a variety of animal models, and more recently, in human patients enrolled in clinical trials.
It has been known for decades that lipid peroxidation detritus of oxidized membrane fats are present in most all diseases of degeneration and aging, including Alzheimer’s disease, Parkinson’s disease, atherosclerosis, ALS, Huntington’s, and fatal inborn genetic errors resulting in neurodegenerative diseases (among others). The hypothesis that controlling such oxidation could provide therapeutic benefit was abandoned when numerous formal trials of classical antioxidants, e.g. Co-enzyme Q, Vitamin E, and others failed to provide meaningful benefit. We believed that the antioxidant mechanism used to attempt control of the membrane oxidation was flawed, but that the target itself was correct. Indeed, by using a new class of oral drugs that are lipids fortified against damage at the key susceptible bonds, we observed reduction in lipid peroxidation damage that halted, and even reversed neurodegenerative disease progression. Dosed in amounts and forms similar to omega 3 and 6 supplements, these drugs exhibited profound disease modification across a broad range of diseases in animal models, placebo controlled- and open label- human trials.
MedicalResearch.com: What are the main findings of prior studies?
Response: A prior phase 1/2 clinical trial in the fatal, neurodegenerative disease of children and young adults, Friedriech’s ataxia, showed that treatment with RT001-a stabilized form of the essential fat linoleic acid—caused a statistically significant reversal of losses in the peak workload patients could generate in a cardiopulmonary exercise test (CPET), supported by improvement trends in other well studied measures of disease progression. https://bit.ly/2qB5CVt Since profound fatigue is the most common complaint among FA patients, improvement in CPET has been accepted by FDA as a primary endpoint for a planned clinical trial
After researchers found in cell and animal models of PLA2G6 deficiency that RT001 could strongly improve cell viability and phenotype, the company responded to two requests for Expanded Access drug treatment in Infantile Neuroaxonal Dystrophy (INAD), a fatal neurodegeneration of infants. INAD is typically diagnosed around 18 months of age, is strictly progressive, and subjects lose all previously gained development milestones and most always die before the age of ten on ventilators and feeding tubes. In the two treated patients, on drug for greater than 6 months or 18 months; respectively, disease progression ceased and even some improvements were noted. Retrotope is starting a formal clinical trial in ultra-rare classical INAD soon.
In other Expanded Access trials, Retrotope has observed improvement in single patient ALS, Late Onset Tay Sachs, and Alzheimer’s ApoE4 patients.
MedicalResearch.com: What should readers take away from your report?
Response: Retrotope is willing to consider physician requests for possible Compassionate Use in diseases in which lipid peroxidation is implicated in the disease etiology, rapid progression and well defined metrics allow measurement of drug effect, and preclinical models or clinical data provide a compelling rationale to treat with D-PUFAs. These trials can help inform decisions about entering randomized controlled trials in the indication.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Retrotope’s drugs, involving stabilization of essential nutrients that become part of critical membrane systems and fortify cells against disease toxins, are a completely new paradigm to address largely intractable diseases of degeneration and aging, and have robust preclinical and clinical data in support of their positive safety and efficacy.
Disclosures: Retrotope is a biopharmaceutical company, and all employees, including this author, have equity positions in the company.
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