Assessing the Safety and Efficacy of ARA 290 in Sarcoidosis Patients with Symptoms of Small Fiber Neuropathy

Sarcoidosis is a condition characterized by the presence of tiny clusters of inflammatory cells in various parts of the body.  Although most commonly observed in the lungs or lymph nodes, sarcoidosis can also affect other organs in the body, including the eyes, skin, and heart^[1].

One of the most common clinical manifestations associated with sarcoidosis is a dysfunction of small nerve fibers that occurs in a patchy, non-length-dependent manner, a condition more commonly known as small fiber neuropathy (SFN). Symptoms of SFN include pins-and-needles, tingling, and numbness; in severe cases, SFN symptoms can include short sensations of shock-like or burning pain, allodynia, and loss of cutaneous sensation and autonomic function.

With the specific cause of sarcoidosis still unknown, and considering recent research demonstrating the prevalence of SFN being grossly underestimated and with no known cure for the condition, Heij et al. developed this randomized double-blind pilot study to examine the safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of SFN.

ARA 290 is a peptide that interacts with the innate repair receptor responsible for initiating cytoprotection, anti-inflammation, and healing. Considering that ARA 290 has been shown to reduce allodynia when tested in preclinical neuropathy models, Heij et. al. hypothesized that patients experiencing symptomatic SFN would benefit from treatment with ARA 290.

To test their hypothesis, the authors of this study enrolled 22 patients diagnosed with sarcoidosis and experiencing symptoms of SFN in either a group receiving intravenous dosing of ARA 290 or a placebo three times a week over the course of a four-week period.

At the conclusion of their study, Heij et al. observed that patients tolerated repeated intravenous infusions of ARA 290 without adverse events. The authors also observed a time-dependent, significant difference between ARA 290 and placebo groups. Specifically, ARA 290 appeared to improve autonomic and pain symptoms associated with SFN, including the severity of dry eyes, blurred vision, and muscle cramps and the severity and frequency of chest pain as assessed by the small fiber neuropathy screening list (SFNSL).

The authors concluded that their study was the first study to demonstrate that ARA 290 appears to be safe when administered repeatedly over a four-week period to sarcoidosis patients with symptoms of SFN with no abnormalities or drug-related adverse effects noted during and after dosing. ARA 290 also appeared to improve the severity and frequency of symptoms associated with SFN while also improving the quality of life and pain for these patients.

Heij et al. indicated that the primary limitations of this trial were the small sample size, patient variability of neuropathic involvement, and lack of skin biopsy or sudomotor testing evidence definitively establishing SFN. The study also demonstrated abnormalities in mechanoreception that prevented the observed reduction in the severity of symptoms as assessed by the SFNL from being fully attributed solely to the effects of ARA 290 on small-fiber function.

The observed reduction of SFN-associated symptoms combined with the acceptable safety demonstrated by frequent administrations of ARA 290 encourages a larger study to examine the potential effects of ARA 290 for sarcoidosis patients with symptoms of small fiber neuropathy.

Source:   (2019, January 30). Sarcoidosis – Symptoms and causes – Mayo Clinic. Retrieved from https://www.mayoclinic.org/diseases-conditions/sarcoidosis/symptoms-causes/syc-20350358

^[1] “Sarcoidosis – Symptoms and causes – Mayo Clinic.” 30 Jan. 2019, https://www.mayoclinic.org/diseases-conditions/sarcoidosis/symptoms-causes/syc-20350358. 19 Aug. 2021.