Selective serotonin reuptake inhibitors (SSRIs) for treatment of COPD

This technology identifies SSRI compounds as potential therapies for treating chronic obstructive pulmonary disease (COPD) via inhibition of cigarette smoke-induced proteolytic enzyme metalloproteinase-1 (MMP-1).

Unmet Need: Targeted therapies for COPD-associated lung destruction

Current therapies for chronic obstructive pulmonary disease (COPD), including bronchodilators and inhaled steroids, primarily manage symptoms and reduce exacerbations but do not directly address the mechanisms driving progressive lung destruction. The lack of effective therapeutic intervention contributes to cycles of chronic pulmonary decline exacerbated by infections, which accelerate the loss of pulmonary architecture and function. There are currently no drugs which directly target these disease driving pathways and can slow pulmonary decline in COPD including disease progression.

The Technology: SSRI-induced MMP-1 inhibition to treat COPD

This technology identifies optimized SSRI compounds as therapeutics for COPD. SSRIs suppress MMP-1 production, a key proteolytic enzyme that initiates inflammation that destroys lung tissue in COPD. The SSRI can be administered either orally, via inhalation, or delivered directly to the lung, where it inhibits cigarette smoke-induced expression of MMP-1, reducing cytokine production and lung damage in vivo. The compounds have been optimized to minimize off target effects and increase efficacy, when compared with commercially available SSRIs used for other indications. As such, this technology has the potential to slow disease progression in patients with COPD.

This technology has been validated in vitro and in vivo in cigarette smoke exposure models.

Applications:

• Therapeutic agent for treating COPD and other lung diseases
• Prophylactic agent for preventing the development of lung disease
• Research model for studying smoke-induced protease production
• Treatment for protease imbalance disorders

Advantages:

• Prevents cigarette smoke-induced lung damage
• Targets underlying mechanisms of COPD
• Can be administered orally, through inhalation, or direct delivery to the lung
• Other SSRIs are already FDA approved for other indications

Lead Inventor:

Jeanine D’Armiento, M.D., Ph.D.

Patent Information:

Patent Pending (US18/596,300)

Related Publications:

• Imai K, Dalal SS, Chen ES, Downey R, Schulman LL, Ginsburg M, D’Armiento JE. “Human collagenase (matrix metalloproteinase-1) expression in the lungs of patients with emphysema.” Am J Respir Crit Care Med. 2001 Mar;163(3): 786-791

• Morishita A, Gerber A, Gow CH, Zelonina T, Chada K, D’Armiento J. “Cell Specific Matrix Metalloproteinase-1 Regulates Lung Metastasis Synergistically with Smoke Exposure.” J Cancer Res Forecast. 2018 Nov 5;1(2)

• Adam G, Shiomi T, Monica G, Jarrod S, Vincent A, Becky M, Tina Z, Jeanine D. “Suppression of cigarette smoke induced MMP1 expression by selective serotonin re-uptake inhibitors.” FASEB J. 2021 Jul;35(7):e21519.

Tech Ventures Reference:

• IR CU14317, CU18044, CU18424, CU21249, CU21262, CU23264

• Licensing Contact: Jerry Kokoshka