$200 million latest gift from mega-philanthropist Len Blavatnik for therapeutics challenge awards fuel translational research

Three research teams have been selected as recipients of the Blavatnik Therapeutics Challenge Awards, an annual awards program that aims to progress promising discovery science at Harvard Medical School toward creating new medicines that could be life-changing for patients.

Open to faculty at the school and its 15 affiliated hospitals, the awards provide critical funding to researchers who’ve made fundamental discoveries with the potential to become powerful clinical interventions.

“We’re living in a prolific time of scientific discovery, and it is our imperative to accelerate the pace of therapeutics research within the HMS community and translate more of our discoveries into new medicines,” said George Q. Daley, dean of HMS.

“The journey from molecule to medicine is long and often requires coordination across several institutions and organizations,” he added. “This critical funding helps us toward our goal.”

Now in its fifth and concluding year, the Blavatnik Therapeutics Challenge Awards have supported 20 research projects. Of the 17 projects awarded in the first 4 years of the program, four have already progressed to either founding a new company or licensing the technology as part of a start-up. Two additional projects may enter clinical trials within the following year.

The 2024 award recipients are:

Addressing Fragile X syndrome through genetics

Principal investigator Jeannie Lee, HMS professor of genetics and pathology at Massachusetts General Hospital

The challenge: The most common inherited cause of autism and intellectual disabilities worldwide, Fragile X syndrome is a genetic disorder that occurs when a single gene located on the X chromosome that is necessary for brain development shuts down. Children with Fragile X syndrome may have speech delays, learning disabilities, or intellectual challenges.

A possible solution: Lee is pursuing a novel approach to treating Fragile X syndrome by reactivating the dormant gene that underlies the condition. As Fragile X syndrome is mainly caused by an expansion of the repeating nucleotide sequence cytosine-guanine-guanine (CGG), Lee’s lab aims to reduce the abnormal CGG repeats. This offers a new strategy for mitigating the syndrome’s neurological impacts.

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Injectable oxygen for life-threatening oxygen deprivation

Principal investigators John Kheir, HMS associate professor of pediatrics at Boston Children’s Hospital, and Yifeng Peng, HMS assistant professor of pediatrics at Boston Children’s Hospital.

The challenge: All living cells require a continuous oxygen supply to maintain structure and function. Even brief episodes that compromise oxygen supply can lead to significant disability and death.

Current approaches, such as supplementing oxygen that a patient breathes or using a ventilator, optimize the function of the lungs. When that is not enough, patients can be supported with ECMO — an external device that directly oxygenates the blood and then returns it to the body. However, ECMO can take up to an hour to institute, and patients can experience life-threatening hypoxia (low oxygen) and organ damage during this time.

A possible solution: Kheir and Peng have developed a potential treatment that allows the direct injection of oxygen gas into the bloodstream to rescue patients in these dire situations.

The oxygen is encapsulated in tiny particles explicitly made for this purpose. The particle shells are manufactured as solid. When injected, the pH of the blood triggers the shells to phase change into fluid, transferring their oxygen cargo to the starved blood and tissues.

In animal models, injection of small amounts of this experimental drug reversed cardiac arrest, improved survival, and dramatically improved survivor outcomes. Funding from the BTCA will support the development of manufacturing techniques to prepare for clinical trials, which will determine whether the treatment is safe and effective for patients.

Targeting Parkinson’s disease at the neurological root

Principal investigator Kevin Hodgetts, HMS associate professor of neurology at Brigham and Women’s Hospital

The challenge: Parkinson’s disease is a lifelong and progressive movement disease affecting seven million people in the United States. Dopamine-boosting (dopaminergic) drugs can temporarily improve symptoms, but there is no cure, and ultimately, patients will deteriorate and succumb to this disease. Genetic studies have shown that the disease involves excess alpha-synuclein protein that results in mitochondrial dysfunction.

A possible solution: With his collaborator Clemens Scherzer of Yale School of Medicine, Hodgetts discovered a druggable target in neurons that reverses this disease process: the β2-adrenoreceptor (β2-AR). The team found that β2-AR agonist drugs—already FDA-approved to treat asthma—reduce alpha-synuclein expression, improve mitochondrial health, and protect neurons in animal models. Multiple population studies have also shown that these drugs reduce the risk of Parkinson’s in humans.

Hodgetts’ team is now developing the next generation of β2-AR agonists—these target β2-ARs located only in the brain, eliminating unwanted side effects outside the central nervous system. The team aims to discover and advance a brain-selective β2-AR agonist through preclinical studies. Should these studies show positive data, the team hopes to advance through to clinical trials—and ultimately bring a new therapeutic for Parkinson’s disease to patients.