JUPITER, Fla.—Alzheimer’s disease, a progressive neurodegenerative disease that erodes thinking and memory and gradually leads to dementia and death, affects about 5.5 million Americans over age 65 and many more under 65. While there are treatments to manage symptoms, no therapies on the market delay symptom progression. Alzheimer’s disease costs the United States about $277 billion per year.
“Once the brain gets damaged, it doesn’t recover, so we want to get to patients before they have Alzheimer’s or at an early stage of the disease,” said Christer Rosén, chairman and CEO of Jupiter Orphan Therapeutics, a clinical-stage drug platform company focused on neurological and rare diseases. In September, the National Institute on Aging at the National Institutes of Health awarded Jupiter $1.76 million over the course of one year to support a Phase 1 clinical study of Jotrol, a potential drug for the treatment of early-stage Alzheimer’s disease. The grant will support a Phase 1 study titled, “Safety and Pharmacokinetics of Jotrol for Alzheimer’s Disease.”
Jotrol, a proprietary patented formulation, features the active ingredient resveratrol. It is a naturally occurring plant compound found in small amounts in red wine, red grapes, berries and peanuts. Rosén explained that “The compound has existed for 50 or 60 years, so it is extremely safe as a natural compound. It has been the subject of 5,000 scientific publications since 2013.”
Multiple clinical studies have determined that resveratrol can reduce markers of brain inflammation and oxidative stress and boost production and function of cells’ energy organelles, called mitochondria. Mitochondrial damage is a feature of Alzheimer’s and other neurodegenerative diseases. Positive resveratrol outcomes in Alzheimer’s disease have stimulated interest because of failures in multiple anti-amyloid trials.
Resveratrol has also been shown to potently activate anti-aging factors called sirtuins, endogenous regulators of metabolism that produce beneficial, caloric restriction-associated amelioration of diseases of aging. Studies of resveratrol suggest that it might reduce age-related cognitive decline as well as Alzheimer’s disease-associated plaques. A daily dose of Jotrol delivers the equivalent resveratrol dose of approximately 20 bottles of red wine—but of course without the side effects of drinking such a large amount of wine.
Which isn’t the same as saying there are no side effects. In earlier clinical studies with resveratrol, there were problems with brain and central nervous system bioavailability at orally tolerated doses. Higher doses have produced gastrointestinal (GI) side effects, such as nausea and diarrhea.
Jupiter Orphan has created the Jotrol delivery platform, enabling resveratrol to be taken in an easily consumable, oral softgel in a patented micellar form. Using the Jotrol platform, resveratrol infuses blood plasma and the central nervous system and crosses the blood brain barrier to unlock the compound’s potential as a therapeutic for neurodegenerative and neurological diseases without the GI issues. By making the drug more soluble in water, Jupiter has also made it more bioavailable. Other than the associated GI side effects at high doses, early clinical studies of regular resveratrol for treatment of Friedreich’s ataxia and Alzheimer’s disease indicated that it was safe and well tolerated.
The formulation has been developed together with Jupiter Orphan’s technology partner, Aquanova AG, and studied in consultation with scientists at the University of Miami, Harvard, MIT and Georgetown University, as well as Australia-based Murdoch Children’s Research Institute, according to Dr. Marshall Hayward, Jupiter’s chief scientific officer.
As he explained, “The NIA award will enable us to take our Jotrol product through Phase 1 and set us up for Phase 2 applications. We have a significant advantage in our development programs, guided by scientific publications on resveratrol, internally developed data, and the open-label studies conducted by MCRI in Friedreich’s ataxia patients, and the Turner et. al. clinical study in 119 Alzheimer’s patients. In that study performed by Georgetown University, resveratrol demonstrated stabilization of key biomarkers.”
According to Rosén, Jupiter Orphan Therapeutics’ long-term focus is to develop a treatment for Alzheimer’s disease, while in parallel developing one or more treatments for rare, “orphan” diseases including Friedreich’s ataxia and mucopolysaccharidosis type-I. Its anti-inflammatory, oxidative stress-reducing and other mechanisms of action enable Jotrol to have multiple potential disease applications, Rosén said, noting, “This can potentially generate a development speed that is very unusual. It means a successful Phase 1 study can generate the ability for rapid initiation of Phase 2 trials in multiple indications, creating strong capital efficiency.”