Constitutive oxalate-biodegrading bacillus subtilis for kidney stones

Ended Project Grant Awarded Last action

Award ID
R43DK133067
Recipient
Awarding agency
Obligated
$942,747

Award facts

Completion date
Place of performance
Laramie, WY, USA

Award details come from USAspending.gov.

Description

Abstract
Kidney stones (nephrolithiasis) are an extremely painful and debilitating condition. About 12% of people will experience kidney stones in their lifetime, and about 70% of those will have recurrences. The economic burden of kidney stones is estimated to exceed $5 billion per year in the USA alone. Each year, over 3 million workdays are lost in the USA due to kidney stones. 75% of kidney stones consist of calcium oxalate (caox), and are caused by excessive urinary oxalate levels. Unfortunately, current treatment options all have serious drawbacks. A low oxalate diet is routinely recommended for caox stone patients, but is not very effective by itself. Alkalinizing agents such as potassium citrate can reduce stone recurrence, but are costly and often cause GI distress. Thiazide diuretics come with frequent, potentially life-threatening adverse effects such as hypokalemia. Thus, there remains a strong need for the development of new kidney stone treatment options that are both safe and effective. We propose to develop and test a new kidney stone treatment consisting of a novel bacillus subtilis strain that overexpresses endogenous oxalate biodegrading enzymes. As bacteria stay in the GUT, the spectrum of potential side effects is massively reduced as compared to small molecule drugs. Thus, our innovative approach is designed to result in an affordable, safe, and broadly effective kidney stone treatment option. In this phase i sbir project, we will develop new bacillus subtilis strains engineered to biodegrade oxalate. We will produce and test different strains to optimize oxalate biodegradation capacity. As we will chromosomally overexpress endogenous enzymes in a spore-forming bacterium, our approach avoids key drawbacks of previously developed oxalate- degrading microbes. Finally, we will determine if the best performing engineered strain can effectively reduce urine oxalate levels in a relevant RAT model.

Transactions

Action Obligated Date
Amendment $0
Amendment $54,965
Amendment $54,965
Amendment $54,965
Amendment $0
Amendment $0
Amendment $0
Amendment $259,284
Amendment $259,284
Original award $259,284

Quick answers

Who received award R43DK133067?

R43DK133067 was awarded to Unlocked Labs Inc. by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on September 15, 2022.

How much is award R43DK133067 worth?

$942,747 has been obligated on R43DK133067.

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