The Cerebral Creatine Deficiency Syndromes (CCDS), are inborn errors of creatine metabolism which include Creatine Transporter Deficiency (CTD) and the two creatine biosynthesis disorders, guanidinoacetate methyltransferase (GAMT) deficiency and L-arginine:glycine amidinotransferase (AGAT) deficiency.

Creatine Transporter Deficiency (CTD, SLC6A8 Deficiency, CRTR) is a rare X-linked inborn error of creatine metabolism, broadly classified as an Autism Spectrum Disorder and form of X-linked intellectual disability and developmental delay. CTD is caused by a defect in the SLC6A8 gene that encodes the creatine transporter protein necessary for the transport of creatine across the blood-brain barrier and across cell membranes. Creatine is taken into cells via the creatine transporter, where it plays an essential role in energy homeostasis, particularly for tissues with high and fluctuating energy demands, such as neurons. Simply put, patients with CTD lack creatine in the brain, which is an essential component of the energy system, and as a result the brain does not have the energy to function properly. This lack of energy results in the clinical signs symptoms of CTD.

Currently, there are no approved treatments for Creatine Transporter Deficiency and patients do not respond to supplementation of creatine monohydrate (unlike the GAMT and AGAT patients, below).

We believe our therapeutic can change the lives of patients with CTD

As CTD is an X-linked disorder, male patients are the most severely affected, but females are carriers of the disease and may be asymptomatic or affected to a lesser degree.



While the exact prevalence of Creatine Transporter Deficiency is unknown, it is estimated that it represents the second largest cause of Autism and X-linked intellectual disability behind Fragile-X syndrome. It is estimated that CTD will represent between roughly 2 and 5% of X-linked intellectual disability, or 1% of all intellectual disability of unknown etiology.

While Creatine Transporter Deficiency is a rare disease, it is Lumos Pharma’s primary focus. Lumos Pharma is proud to serve the CTD community.

Typically, Creatine Transporter Deficiency patients will begin the diagnostic process when the patient begins to miss standard developmental milestones around age 1 or 2. A preliminary screen for an elevated Creatine/Creatinine ratio in urine should be conducted if CTD is suspected. Lumos believes that this simple screen should be conducted for all patients with Autism and/or intellectual disability of unknown etiology. Finally, a confirmatory genetic test or proton magnetic spectroscopy (MRS) test examining creatine levels in the brain should be conducted.

Please see your physician or pediatric neurologist immediately if CTD is suspected.

GAMT and AGAT are errors of creatine metabolism, resulting in a defect in the synthesis of creatine altogether. Due to the creatine biosynthesis error, GAMT and AGAT patients lack creatine in both the periphery and central nervous system, and maintain a functional creatine transporter system.

GAMT and AGAT share many of the clinical symptoms as CTD. These patients respond reasonably well to supplementation of creatine monohydrate and certain dietary modifications.

GAMT and AGAT are extremely rare disorders.


LUM-001 is a repurposed small molecule that is biochemically similar analog of creatine and has shown promising therapeutic potential for the treatment of Creatine Transporter Deficiency in preclinical studies. LUM-001 is a small and planar molecule with the chemical characteristics necessary to cross membranes.

Lumos Pharma’s academic partners at the University of Cincinnati conducted a knockout mouse study examining the efficacy of LUM-001 for the Treatment of CTD. The SLC6A8 gene was efficiently deleted in the knockout mice, which resulted in an absence of creatine in the brain due to dysfunction of the transporter, and the mice closely mimicked the human phenotype of the disease. The untreated knockout mice exhibited impaired cognitive function, but normal balance and musculoskeletal control systems.

In the knockout mice treated with LUM-001, LUM-001 was shown to cross the blood-brain barrier, be phosphorylated and dephosphorylated by both mitochondrial and cytosolic creatine kinases, and substantially improved cognitive function in spatial learning and memory and novel object recognition tests.

The knockout mice were also treated with creatine and placebo with no cognitive improvement, as was expected.

Lumos Pharma is optimistic that this research will translate to human patients in a clinical setting and provide a much needed therapeutic for patients with CTD and their families.

Lumos Pharma intends to develop LUM-001 as a treatment for Creatine Transporter Deficiency. LUM-001 is a repurposed molecule, having been studied in a previously filed Investigational New Drug (IND) application for use in a solid tumor indication. LUM-001 has a strong safety profile, as indicated by the earlier IND, however, Lumos Pharma is required to repeat some preclinical studies in an oral formulation, as the previous IND studied LUM-001 in an IV formulation.