A groundbreaking approach to treating chemotherapy-induced peripheral neuropathy offers new hope for cancer patients
For millions of cancer patients worldwide, the journey through treatment brings an unexpected adversary—not just the disease itself, but the often debilitating side effects of the very medications designed to save them.
of chemotherapy patients develop peripheral neuropathy
affected worldwide by chemotherapy side effects
treatment options currently available
Chemotherapy-induced peripheral neuropathy (CIPN) represents one of the most challenging complications of cancer treatment, affecting approximately 30-40% of patients undergoing chemotherapy. This nerve damage can manifest as pain, tingling, numbness, and weakness, primarily in the hands and feet, sometimes becoming so severe that treatment regimens must be altered or discontinued.
Until recently, options for preventing or treating CIPN have been limited, leaving patients to choose between continuing life-saving cancer treatment or preserving their quality of life. However, a groundbreaking development from Stony Brook University researchers is poised to change this difficult calculus, offering new hope through a novel biological pathway.
Peripheral neuropathy occurs when the nerves located outside of the brain and spinal cord—the peripheral nerves—become damaged. In the context of chemotherapy, certain cancer drugs are particularly notorious for causing this damage, including platinum-based drugs, taxanes, vinca alkaloids, and others.
What makes these treatments especially challenging is that the nerve damage can persist long after cancer treatment has concluded, becoming a chronic condition that significantly diminishes quality of life.
The biological mechanism behind CIPN has remained somewhat elusive, hampering the development of effective treatments. What scientists do understand is that chemotherapy drugs can directly damage nerve cells, disrupt mitochondrial function in neurons, and trigger inflammatory responses that exacerbate nerve injury.
The revolutionary approach emerging from Stony Brook University research focuses on a different biological system entirely—the endocannabinoid system, specifically through Fatty Acid Binding Proteins (FABPs).
The endocannabinoid system, named after the cannabis plant that led to its discovery, is a complex cell-signaling system that plays a role in regulating a range of functions including sleep, mood, appetite, memory, reproduction, and, importantly, pain perception.
Within this system, researchers identified that FABPs, particularly FABP5, serve as intracellular transporters for the endocannabinoid anandamide (AEA), a neurotransmitter naturally produced in the brain that binds to cannabinoid receptors .
Think of FABPs as specialized delivery vehicles that shuttle anandamide to sites where it can be broken down. When FABP5 is overactive, it transports anandamide too efficiently to degradation sites, reducing its pain-relieving effects.
By inhibiting FABP5, researchers hypothesized they could enhance the body's natural pain-relief mechanisms precisely where needed.
This groundbreaking discovery was spearheaded by Drs. Iwao Ojima, Martin Kaczocha, and Dale Deutsch at Stony Brook University's Institute of Chemical Biology & Drug Discovery (ICBⅅ) . Their collaborative work, bridging departments of chemistry, anesthesiology, and biochemistry, exemplifies the interdisciplinary approach necessary for tackling complex biomedical challenges.
The culmination of this research is ART26.12, a selective FABP5 inhibitor compound that has shown remarkable promise in preclinical studies for treating neuropathic pain without the addictive potential of opioids .
FDA clearance of IND application allowing first-in-human studies to begin
Safety Review Committee recommendation approved advancement to next dose level based on initial safety data
International Phase 1 trials launch with expanded testing across global sites
Targets the underlying biological pathway rather than just masking symptoms
Offers pain relief without the addiction risks of traditional opioids
Could enable more patients to complete chemotherapy without dose reductions
| Treatment Type | Mechanism of Action | Advantages | Limitations |
|---|---|---|---|
| Traditional Antidepressants/Anticonvulsants | Modulate neurotransmitter systems | Well-established safety profiles | Limited efficacy, significant side effects |
| Opioids | Activate opioid receptors in brain and spinal cord | Powerful pain relief | High addiction potential, respiratory depression risk |
| ART26.12 (FABP5 Inhibitor) | Enhances body's natural endocannabinoid system | Non-addictive, targets underlying mechanism | Still in clinical trials, long-term effects unknown |
The development of ART26.12 and similar advanced therapeutics relies on sophisticated research tools and methodologies. Below are some essential components of the modern chemical biologist's toolkit for drug discovery and development.
Specifically block target protein activity. ART26.12 selectively inhibits FABP5 to enhance endocannabinoid signaling.
High-resolution imaging of protein structures. Enables visualization of FABP-inhibitor interactions at atomic level.
Non-invasive imaging of biological processes. Tracks drug distribution and target engagement in living organisms.
Highly specific binding to target molecules. Used in pre-targeting strategies for advanced therapies.
While ART26.12's initial application targets chemotherapy-induced peripheral neuropathy, the implications of FABP research extend far beyond this single condition. The endocannabinoid system modulates diverse physiological processes, suggesting potential applications for FABP inhibitors in treating inflammation, neurological conditions, and even cancer itself .
Potential applications in Alzheimer's, Parkinson's, and other neurodegenerative diseases.
Modulating inflammatory responses in conditions like rheumatoid arthritis and IBD.
Potential direct anti-cancer effects through modulation of cancer cell signaling.
The expanding potential of this research is reflected in the diverse expertise being recruited to the ICB&DD. Recent additions to the institute include:
Pioneers novel models in structural and computational molecular biophysics
Employs PET imaging to study neurochemical alterations in mental illness
Uses cryo-electron microscopy to understand molecular mechanisms
The development of ART26.12 represents a convergence of basic scientific discovery and targeted therapeutic innovation.
From the fundamental recognition of FABPs as regulators of the endocannabinoid system to the precise engineering of a selective inhibitor, this journey exemplifies the potential of chemical biology to address pressing medical challenges.
While much work remains before ART26.12 might become available to patients, its progression through clinical trials marks a significant step toward addressing the silent suffering of chemotherapy-induced peripheral neuropathy. More broadly, it signals a shift in pain management away from simply blocking pain signals and toward modulating the body's inherent regulatory systems.
these advances offer not just hope for future treatments, but validation of their struggle and the promise of more compassionate science to come.
This article is the tenth in a series exploring the groundbreaking work of chemical biology and drug discovery institutes worldwide. For previous installments, please visit our online archive.