Addressing proteotoxic diseases, big and small

Things don’t work well when
they’re clogged with debris.

This is especially true for
the cells in the body.

We have an approach


An astonishing number of proteins are processed and travel through the endoplasmic reticulum in our cells. If these aggregates aren’t cleaned up, the result can be any number of debilitating diseases.

The primary focus at Jace Biomedical (JBI) is to alleviate the burden caused by these proteotoxic diseases. By precisely increasing the degredation of only the proteins in the endoplasmic reticulum, we resolve the aggregation of toxic proteins while avoiding side-effects that would result from upregulating protein breakdown in the whole cell.


The Problem: Proteotoxic Diseases

The endoplasmic reticulum (ER) processes all proteins in our cells that are membrane bound, are destined for organelles, that are secreted and/or that require a variety of post translational modification. With such a large volume and variety of proteins going through this organelle, it’s no surprise that sometimes things go wrong: proteins harbor deleterious mutations, protein production is increased beyond the ER’s capacity to effectively handle, or degredation is slowed to sub-optimal rates. All of these possibilities have the potential to result in the destructive build-up of protein.

When things go particularly poorly, our cells simply can’t keep up. Proteins clump together, crippling the cell’s ability to carry out basic functions. In many cases, cells are damaged past the point of possible recovery and cells die. In this case the only recourse is to create more cells. Unfortunately, this type of regeneration is not something that all organs do very well. Furthermore, these aggregates can be secreted outside the cell, causing further damage.

This kind of protein-aggregation has been linked to a variety of ailments including:


  • Neurodegenerative Diseases
  • Cardiovascular Disease
  • Metabolic Disorders
  • Musculoskeletal Diseases
  • Some Cancers

This kind of protein-aggregation has been linked to a variety of ailments including:

Neurodegenerative Diseases


Cardiovascular Diseases


Metabolic Disorders


Musculoskeletal Diseases


(Photo Above) Protein degradation is inhibited by acetylation of specific proteins in the ER:

Quality control mechanisms in the ER downregulate autophagy through the acetylation of Atg9A by two recently discovered acetyltransferases (ATase1 and ATase2). Our approach uses small molecules to target proteins in this pathway and release inhibition of autophagy, leading to increased degradation of toxic protein aggregates.

Our Approach

Our Solution: Regulate Autophagy in the ER

Cells degrade misfolded, aggregated or unnecessary proteins through the process of autophagy. Autophagy specific to the ER is known as reticulophagy. Reticulophagy is regulated through quality control that is signaled through a recently discovered mechanism of protein acetylation in the ER.

Our lead program uses small molecules to intervene at this quality control checkpoint, turning the dial to upregulate reticulophagy and breakdown toxic protein aggregates residing and being formed specifically in the ER.

Our Drug Development Engine is a Real Workhorse

JBI is building a therapeutic pipeline. Initially this approach was developed as an intervention for the incredibly burdensome Alzheimer’s disease (AD). Since then, research efforts have identified multiple diseases that result from protein aggregation through the secretory pathway. In this way, our interventional approach targeting this same pathway can serve to remedy a wide host of ailments. We continue to identify diseases for which our company is uniquely positioned to address with this novel solution.

Backed by Science

Want to learn more? Here’s a good place to start

Journal of Cell Science – 2018
Nε-lysine acetylation on in the endoplasmic reticulum – a novel cellular mechanism that regulates proteostasis and autophagy

Aging Cell – 2018
Increased transport of acetyl-CoA into the endoplasmic reticulum causes a progeria-like phenotype

Brain, A Journal of Neurology – 2016
Improved proteostasis in the secretory pathway rescues Alzheimer’s disease in the mouse
& Scientific Commentary: Targeting endoplasmic reticulum acetylation to restore proteostasis in Alzheimer’s disease

Journal of Neuroscience – 2014
Deficient import of acetyl-CoA into the ER lumen causes neurodegeneration and propensity to infections, inflammation, and cancer

Biochimica et Biophysica Acta (BBA) – Molecular Cell Research – 2013
Lysine acetylation in the lumen of the ER: A novel and essential function under the control of the UPR

Journal of Biological Chemistry – 2013
SLC33A1/AT-1 regulates the induction of autophagy down-stream of IRE1/XBP1

Journal of Biological Chemistry – 2012
Biochemical inhibition of the acetyltransferases ATase1 and ATase2 reduces β-secretase (BACE1) levels and Aβ

Journal of Cell Science – 2010
AT-1 is the ER membrane acetyl-CoA transporter and is essential for cell viability

About Jace Biomedical, Inc.


JBI is a small but growing pharmaceutical company founded by two veterans of the industry, Carl Horn and Deborah Milkowski, PhD. Our focus is developing novel therapies for proteotoxic diseases of the secretory pathway that have no or limited therapeutic options.

After working together for several years at TAP Pharmaceuticals strategically building its pipeline, Mr. Horn and Dr. Milkowski once again joined forces in recent years. They began collaborative discussions with Dr. Luigi Puglielli from the University of Wisconsin Madison to explore the potential of translating his novel research into a groundbreaking treatment for millions of patients afflicted with Alzheimer’s disease. Since then, our pipeline of therapeutic indications has rapidly expanded.

Our Future

Since it’s founding, the focus of JBI has expanded substantially. As research has progressed, a variety of diseases resulting from protein aggregation in the secretory pathway have come to light. We continue to explore how JBI can intervene in these diseases.

We are excited about our future and believe that our technology can make a genuine impact in the lives of many. We’re poised to move forward and are anxious to meet our goals. Our immediate priorities include compound optimization and pre-IND studies with the longer-term goals of clinical trials and moving into patients.

If you are interested in learning more about ways you can partner with us to reach these milestones, we’d love to hear from you.


Carl Horn, Founder

Carl Horn brings over 25 years of pharmaceutical, diagnostic and biotech experience to JBI. Prior to JBI, he served as Senior Vice President, Corporate and Business Affairs at Therapeutic Proteins International, LLC (TPI). At TPI, Carl successfully guided the company through its acquisition by Amneal Enterprises, LLC.

Prior to TPI, Carl was General Manager Global Export Business for Takeda International. Prior to Takeda, Carl led the business development function at TAP Pharmaceuticals for seven years. Previously, Carl worked at Abbot Laboratories in marketing and strategic planning leadership positions.

Deborah Milkowski, Phd, Founder

Dr. Milkowski has more than 13 years of industry experience in senior roles at TAP Pharmaceuticals where she was the Director of the Pharmacology and Technical Assessment organizations.

Dr. Milkowski oversaw the pharmacology sections of 10 IND and 4 NDA submissions, including approvals for Lupron Depot® and Uloric®.

She was responsible for the safety and efficacy pharmacology for all development compounds as well as for the technical feasibility assessment of all in-licensed technology. Dr. Milkowski received her PhD in Molecular Biology and Biochemistry from Northwestern University Medical School.


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