How Prader-Willi Syndrome (PWS)
Bone is a dynamic organ, is continually being laid down through modeling and renewed in a process called remodeling (see diagram). Bone modeling and remodeling are naturally occurring processes and are responsive to local and hormonal signals. Bone can become compromised when the modeling or remodeling process is out of balance, resulting in the potential for deformation, fragility and fractures.
In children with PWS, the skeleton is affected by abnormal endocrine signals and deficient “crosstalk” between muscles and bones. These patients exhibit low bone mineral density (BMD) as early as the teen years. Without treatment, the bone issues can constrain mobility, vitality and overall well-being in PWS patients, beginning in young children. Beryl’s entry to this arena marks an exciting offering of hope.
The Bone Remodeling Process
In a complex multi-site process, old bone is resorbed and replaced by new bone.
Left to right: Yossi Tam, DMD, PhD, Raphael Mechoulam, PhD, Co-Founders Lisa Padilla and Allison Drew Klein
The Science Story
Lipids Are Important in Management of Bone Health
Historically, lipids have been known to function in energy storage or as structural determinants of the cell membrane. A role as signaling molecules in physiological and pathological processes was recently identified and the regulation of bone mass was identified as a target.
Fatty acids are a family of naturally occurring lipids. Oleoyl Serine (OS) is a fatty acid derivative found in many tissues, including bone; it is produced locally and supports bone formation as well as bone resorption. OS is a Fatty Acid Amide (FAA) that is an endogenous modulator of bone remodeling.
Preventative Benefits of
HU-671 in Experimental
Researchers at Hebrew University developed derivatives of OS including HU-671 and showed in animal models that low BMD and mechanical strength were improved by treatment with compounds in the FAA family. A benefit of treatment with Beryl FAAs was shown in a model of Prader-Willi syndrome. The experimental results showed prevention of the bone manifestations in the test model.
In a separate study, reduced blood serum levels of OS were seen in individuals with PWS. DEXA analysis Z scores showed reduced BMD in individuals with PWS, which was positively correlated with serum OS levels at multiple sites, i.e., femoral neck, total hip, lumbar spine, and forearm.
The association between FAA deficiency and low BMD suggests that Beryl FAAs may provide a solution for PWS patients.
Bone remodeling consists of two actions: bone breakdown and bone build-up. Almost all of the therapeutics on the market today work on one side of the equation or the other. Also, due to unwanted medical issues, current market options may be used only for a limited time. Our compound, which is already found in our bodies, works on both sides of the bone remodeling equation and is found in food products, has a potentially attractive efficacy and safety profile.
has exclusive worldwide rights to unique, patented small molecules that work in two ways:
Maximizing peak bone mass. Avoids the breakdown and decreased bone accrual that impacts bone development in Prader-Willi Syndrome pediatric patients, inhibiting natural growth.
Beryl will pursue this PWS pediatric opportunity first, and will then pursue other rare pediatric diseases that affect low bone mass and bone fragility diseases.
Works to recover bone and improve bone mineral density lost in the natural aging process, which leads to osteoporosis.