Patients who have the rare genetic disorder cerebral adrenoleukodystrophy have few options to stave off the progressive decline of brain and muscle function. Within three to five years of diagnosis, the disease typically becomes fatal.
A startup called NeuroVia has developed a drug that it says treats the metabolic defects that lead to the disease’s symptoms. As the Cambridge, MA-based biotech prepares for more clinical tests of its pill, it has closed on $14 million in financing. Novartis Venture Fund and Sanofi-Genzyme BioVentures co-led the Series A round, which also included investments from BioMed Ventures and Enso Ventures.
Leukodystrophies are metabolic diseases caused by genetic abnormalities. The progression of these diseases affect the brain, spinal cord, and peripheral nerves, according to the National Organization for Rare Disorders. The most common leukodystrophy, X-linked adrenoleukodystrophy (ALD), is caused by a defect in the ABCD1 gene on the X chromosome. This form of the disease, which affects the nervous system and the adrenal glands, affects one in every 20,000 to 50,000 people.
Patients diagnosed with ALD currently have two treatment options. Lorenzo’s Oil, a combination of extracts from olive and rapeseed oils, reduces the levels of damaging fatty acids that lead to the progression of the disease. But the nonprofit The Stop ALD Foundation notes that while some studies suggest the oil holds off the onset of ALD, the research does not prove the treatment was what prevented development of symptoms. The FDA considers Lorenzo’s Oil experimental.
The other treatment option is a stem cell transplant. Though these transplants can slow the progress of the disease, they can’t repair the damage that has already been done, according to Stop ALD. But stem cell transplants don’t always work, and they also come with the risk of potential complications, some of which can become fatal.
NeuroVia is not the only company trying to develop a better ALD treatment. Cambridge-based BlueBird Bio (NASDAQ: BLUE) is testing a gene therapy that, if it works, would offer a long-lasting treatment for the disease that avoids the risks of a stem cell transplant. The experimental treatment, which BlueBird calls Lenti-D, uses a virus to deliver the proper genetic instructions to a patient’s defective genes in order to fix them. This gene therapy is currently in a Phase 2/3 clinical trial.
NeuroVia’s scientific founder is Thomas Scanlan, a professor at Oregon Health & Science University whose research focuses on thyroid hormone action. NeuroVia’s drug NV1205 is sobetirome, a synthetic form of a thyroid hormone. Sobetirome has already been studied in weight loss, as well as in potential applications treating metabolic disorders. That research includes applications of the compound in leukodystrophies.
ALD patients have high concentrations of very long-chain fatty acids because their defective gene prevents them from making a normal form of the protein that breaks these fatty acids down, according to the National Organization for Rare Disorders. The buildup of these fatty acids damages myelin, the coating that protects nerves. NeuroVia has published preclinical trial results showing that its drug reduced levels of very long chain fatty acids in the brains, blood, and adrenal tissues of mice.
Now, NeuroVia wants to show that its approach can reduce levels of the fatty acid in humans. So far, the company has completed a Phase 1 study testing a range of doses of its drug. With the new capital, NeuroVia is planning a Phase 1/2 clinical trial that will continue testing various doses before proceeding to long-term treatment. According to records the company filed on clinicaltrials.gov, the two-year open-label study aims to enroll 25 boys between 4 and 18 in age.
Though ALD is mostly found in children, symptoms don’t develop in some patients until adulthood. There are six different types of ALD, categorized by symptoms and the patient’s age at the disease’s onset. NeuroVia says its drug could offer a treatment for all types of ALD.