Grapes of Health

John Steinbeck’s epic novel, Grapes of Wrath, captures the pilgrimage of the Joad family from Oklahoma to California and their individual and collective struggles along the journey. Steinbeck could easily write a similar saga titled Grapes of Health for a molecule from grapes that is being targeted for treating rare diseases.

Severe drought mixed with dust storms that smothered agriculture and killed livestock from Texas through much of the lower plains states. These factors were two of many compounding factors that fueled the Great Depression, and caused farmers and agriculture workers – like the Joad family in Grapes of Wrath – to migrate west in order to continue their heritage of farming.

Similarly, several clinical trials using a molecule called resveratrol failed, which also led many companies to abandon resveratrol and move to other potential therapies, but some stayed.

Resveratrol is sought for its gene regulating capability that not only increases mitochondria, but also increases the density of cristae within existing mitochondria. Cristae give a mitochondrion the ability to proportionately produce more ATP as cristae density increases.

“As mitochondria are the powerhouse of the each cell, their numbers are key to ensuring homeostasis for the cell,” explained Christer Rosen, CEO of Jupiter Orphan Therapeutics.

“In terminal diseases, one notable hallmark is the loss of mitochondria and the dysregulation of existing mitochondria,”

“But resveratrol has the capability to reverse that as we have been able to show in animals.”

CheckOrphan met with Jupiter Orphan at BioEurope to discuss their clinical programs focusing on rare diseases.

Liver Metabolism and Solubility

Resveratrol comes with two problems when trying to use it therapeutically, and the first comes with a “word to the wise” warming for those who take it as a supplement.

“It is difficult to get resveratrol in a formulation that will allow resveratrol to be absorbed in the body…over the counter supplements don’t do anything to solve that problem.”

“Then, once inside, you have the problem of liver metabolism, which can eliminate what little enters the body before it can reach the area in the body.”

Again, a plot where many researchers have endured “grapes of wrath”.

“But we have changed all that. We have been able to ensure resveratrol not only enters the body by over 20 fold, but we are also ensuring enough reaches the brain.”

The latter part is key for Jupiter Orphan’s quest to treat Friedrich Ataxia (FA), mucopolysaccaridosis type 1 (MPS1) and MELAS, which are all in clinical trials.

Jupiter Orphan’s most advanced clinical program is with FA.

Grapes of Health – Mechanisms of Action

Resveratrol has long been heralded as a possible fountain of youth, or more appropriately – and anti-aging option. It has noted antioxidant properties, which factor in its ability to change disease pathology, but even more notable is its action on a family of proteins that regulate key gene expression and activation, called Sirtuins.

Researchers have also shown that Resveratrol improves mitochondrial function and prevention and/or treatment human physiological diseases through its ability to activate key regulators: AMPK, PGC-1α, and SIRT1, which are the main drivers of the mitochondrial biogenesis.

Another key mechanism of action of resveratrol is its ability to block Nrf2, which plays a key role in activating the NLRP3 inflammasome. The NLRP3 inflammasome plays a key role in many metabolic diseases.

 “It has been a long journey and we are excited to have a formulation that can help resveratrol reach its full potential in humans that we – and the independent science community – has seen in animals.”