Featured Publications

Engineered CRISPR-Base Editors as a Permanent Treatment for Familial Dysautonomia

Pre-printed at bioRxiv 2025

Key Takeaway: Development of a precise CRISPR-based therapeutic approach to correct the splicing defects causing familial dysautonomia (FD), a severe neurological disorder. This study provides the foundation for a transformative treatment for this devastating disease.

In vivo Treatment of a Severe Vascular Disease via a Bespoke CRISPR-Cas9 Base Editor

Pre-printed at bioRxiv 2025 - accepted at Nature Biomedical Engineering

Key Takeaway: This study highlights how customized CRISPR-Cas enzymes can enhance on-target correction while minimizing bystander edits, culminating in a precise editing approach that may enable a long-lasting treatment for patients with vascular diseases.

Optimization of base editors for the functional correction of SMN2 as a treatment for spinal muscular atrophy 1

Nature Biomedical Engineering 2023

Key Takeaway: We developed an optimized base editing strategy to efficiently and safely introduce therapeutic modifications in the SMN2 gene as a potential treatment for spinal muscular atrophy (SMA), independent of individual genetic mutations. This approach holds promise for broader application across a range of human diseases.

See also: Behind the Paper & MGH Press Release & CRISPR Medicine News

Previously pre-printed in bioRxiv

Serum creatinine is a biomarker of progressive denervation in spinal muscular atrophy

Neurology 2020

Key Takeaway: Serum creatinine levels reflect spinal muscular atrophy (SMA) disease severity, suggesting that creatinine is a candidate biomarker for SMA progression and these simple measurements should be included in the routine analysis of all patients with SMA.

TGF-β2 is an exercise-induced adipokine that regulates glucose and fatty acid metabolism

Nature Metabolism 2019

Key Takeaway: This study reveals a mechanism by which exercise training regulates whole-body metabolic homeostasis and provides new insight into adipose–muscle tissue cross-talk as a key axis to counteract metabolic diseases.

Publications

2020-2025

Spellman RG, Ha LL, Da Silva Duarte Lepez S, Arruda EA, Rodrigues E, Swoboda KJ, Alves CRR. Early life safety profiling of gene therapy for spinal muscular atrophy. Gene Ther. 2025 Apr 1. doi: 10.1038/s41434-025-00529-6. 

Alves CRR, Das S, Krishnan V, Ha LL, Fox LR, Stutzman HE, Shamber CE, Kalailingam P, McCarthy S, Lino Cardenas CL, Fong CE, Imai T, Mitra S, Yun S, Wood RK, Benning FMC, Lawton J, Kim N, Silverstein RA, da Silva JF, de la Cruz D, Richa R, Malhotra R, Chung DY, Chao LH, Tsai SQ, Maguire CA, Lindsay ME, Kleinstiver BP, Musolino PL. In vivo Treatment of a Severe Vascular Disease via a Bespoke CRISPR-Cas9 Base Editor. bioRxiv [Preprint]. 2024 Nov 11:2024.11.11.621817. doi: 10.1101/2024.11.11.621817

Yun S, Chekuri A, Art J, Kondabolu K, Slaugenhaupt SA, Zeltner N, Kleinstiver BP, Morini E, Alves CRR. Engineered CRISPR-Base Editors as a Permanent Treatment for Familial Dysautonomia. bioRxiv [Preprint]. 2024 Dec 20:2024.11.27.625322. doi: 10.1101/2024.11.27.625322.

das Neves W, Alves CRR, Dos Santos G, Alves MNN, Deik A, Pierce K, Dennis C, Buckley L, Clish CB, Swoboda KJ, Brum PC, de Castro Junior G. Physical performance and plasma metabolic profile as potential prognostic factors in metastatic lung cancer patients. Eur J Clin Invest. 2024 Nov;54(11):e14288. doi: 10.1111/eci.14288.

Tobias GC, Gomes JLP, Fernandes LG, Voltarelli VA, de Almeida NR, Jannig PR, de Souza RWA, Negrão CE, Oliveira EM, Chammas R, Alves CRR, Brum PC. Aerobic exercise training mitigates tumor growth and cancer-induced splenomegaly through modulation of non-platelet platelet factor 4 expression. Sci Rep. 2023 Dec 11;13(1):21970. doi: 10.1038/s41598-023-47217-2.

Alves CRR*, Ha LL, Yaworski R, Sutton ER, Lazzarotto CR, Christie KA, Reilly A, Beauvais A, Doll RM, de la Cruz D, Maguire CA, Swoboda KJ, Tsai SQ, Kothary R, Kleinstiver BP*. Optimization of base editors for the functional correction of SMN2 as a treatment for spinal muscular atrophy. Nature Biomedical Engineering. 2023 Dec 06. doi: 10.1038/s41551-023-01132-z. *co-corresponding authors

Silva Rodrigues G, Noronha NY, de Almeida ML, Sobrinho ACDS, Watanabe LM, Pinhel MAS, de Lima JGR, Zhang R, Nonino CB, Alves CRR*, Bueno Jr CR*. Exercise training modifies the whole-blood methylation profile in middle-aged and older women. J Appl Physiol. 2023 Jan 26. doi: 10.1152/japplphysiol.00237.2022. *These authors contributed equally to this work

Farrar MA, Groen E, Alves CRR. Circulating neurofilaments to track dorsal root ganglion toxicity risks with AAV-mediated gene therapy. Mol Ther Methods Clin Dev. 2022 Jun 20;26:96-97. doi: 10.1016/j.omtm.2022.06.005.

Alves CRR*, Goodyear LJ, Brum PC*. Muscle metabolic stress determines cancer cachexia severity in mice. Front Physiol. 2022 Nov 28;13: 1033932. doi: 10.3389/fphys.2022.1033932. *co-corresponding authors

Kusuyama J, Makarewicz NS, Albertson BG, Alves-Wagner AB, Conlin RH, Prince NB, Alves CRR, Ramachandran K, Kozuka C, Xiudong Y, Xia Y, Hirshman MF, Hatta T, Nagatomi R, Nozik ES, Goodyear LJ. Maternal Exercise-Induced SOD3 Reverses the Deleterious Effects of Maternal High Fat Diet on Offspring Metabolism Through Stabilization of H3K4me3 and Protection Against WDR82 Carbonylation. Diabetes. 2022 Mar 15:db210706. doi: 10.2337/db21-0706.

Magen I, Aharoni S, Yacovzada NS, Tokatly Latzer I, Alves CRR, Sagi L, Fattal-Valevski A, Swoboda KJ, Katz J, Bruckheimer E, Nevo Y, Hornstein E. Muscle microRNAs in the cerebrospinal fluid predict clinical response to nusinersen therapy in type II and type III spinal muscular atrophy patients. Eur J Neurol. 2022 Aug;29(8):2420-2430. doi: 10.1111/ene.15382. 

Alves CRR, Petrillo M, Spellman R, Garner R, Zhang R, Kiefer M, Simeone S, Sohn J, Eichelberger EJ, Rodrigues E, Arruda EA, Townsend EL, Farwell W, Swoboda KJ. Implications of circulating neurofilaments for spinal muscular atrophy treatment early in life: A case series. Mol Ther Methods Clin Dev. 2021 Oct 30;23:524-538. doi: 10.1016/j.omtm.2021.10.011.

Alves CRR*, Eichelberger EJ, das Neves W, Ribeiro MAC, Bechara LRG, Voltarelli VA, de Almeida NR, Hagen L, Sharma A, Ferreira JCB, Swoboda KJ, Slupphaug G, Brum PC*. Cancer-induced muscle atrophy is determined by intrinsic muscle oxidative capacity. FASEB J. 2021 Jul;35(7):e21714. doi: 10.1096/fj.202100263R. *co-corresponding authors

Eichelberger EJ, Alves CRR, Zhang R, Petrillo M, Cullen P, Farwell W, Hurt JA, Staropoli JF, Swoboda KJ. Increased systemic HSP70B levels in spinal muscular atrophy infants. Ann Clin Transl Neurol. 2021 May 15. doi: 10.1002/acn3.51377.

das Neves W, Alves CRR, de Souza Borges AP, de Castro G Jr. Serum Creatinine as a Potential Biomarker of Skeletal Muscle Atrophy in Non-small Cell Lung Cancer Patients. Front Physiol. 2021 Apr 12;12:625417. doi: 10.3389/fphys.2021.625417.

Nigro P, Middelbeek RJW, Alves CRR, Rovira-Llopis S, Ramachandran K, Rowland LA, Møller AB, Takahashi H, Alves-Wagner AB, Vamvini M, Makarewicz NS, Albertson BG, Hirshman MF, Goodyear LJ. Exercise Training Promotes Sex-Specific Adaptations in Mouse Inguinal White Adipose Tissue. Diabetes. 2021 Feb 9:db200790. doi: 10.2337/db20-0790.

Siranosian JJ, Nery FC, Alves CRR, Siranosian BA, Lyons NJ, Eichelberger EJ, Garner R, Da Silva Duarte Lepez S, Johnstone AJ, Subramanian A, Swoboda KJ. Whole-blood dysregulation of actin-cytoskeleton pathway in adult spinal muscular atrophy patients. Ann Clin Transl Neurol. 2020 Jul;7(7):1158-1165. doi: 10.1002/acn3.51092

Alves CRR, Zhang R, Johnstone AJ, Garner R, Eichelberger EJ, Lepez SDSD, Yi V, Stevens V, Poxson R, Schwartz R, Zaworski P, Swoboda KJ. Whole blood survival motor neuron protein levels correlate with severity of denervation in spinal muscular atrophy. Muscle Nerve. 2020 Sep;62(3):351-357. doi: 10.1002/mus.26995

Alves CRR*, Neves WD, de Almeida NR, Eichelberger EJ, Jannig PR, Voltarelli VA, Tobias GC, Bechara LRG, de Paula Faria D, Alves MJN, Hagen L, Sharma A, Slupphaug G, Moreira JBN, Wisloff U, Hirshman MF, Negrão CE, de Castro G Jr, Chammas R, Swoboda KJ, Ruas JL, Goodyear LJ, Brum PC*. Exercise training reverses cancer-induced oxidative stress and decrease in muscle COPS2/TRIP15/ALIEN. Molecular Metabolism. 2020 Sep;39:101012. doi: 10.1016/j.molmet.2020.101012. *co-corresponding authors

Alves CRR, Zhang R, Johnstone AJ, Garner R, Nwe PH, Siranosian JJ, Swoboda KJ. Serum creatinine is a biomarker of progressive denervation in spinal muscular atrophy. Neurology. 2020 Mar 3;94(9):e921-e931. doi: 10.1212/WNL.0000000000008762

2020 and older

Alves CRR. Exercise training: thinking ahead to counteract systemic manifestations of spinal muscular atrophy. J Physiol. 2019 Dec;597(24):5757-5758. doi: 10.1113/JP279033 

Nery FC, Siranosian JJ, Rosales I, Deguise MO, Sharma A, Muhtaseb AW, New P, Johnstone AJ, Zhang R, Fatouraei M, Huemer N, Alves CRR, Kothary R, Swoboda KJ. Impaired kidney structure and function in spinal muscular atrophy. Neurol Genet. 2019 Aug 12;5(5):e353. Doi: 10.1212/NXG.0000000000000353

Alves CRR, MacDonald TL, Nigro P, Pathak P, Hirshman MF, Goodyear LJ, Lessard SJ. Reduced sucrose nonfermenting AMPK-related kinase (SNARK) activity aggravates cancer-induced skeletal muscle wasting. Biomed Pharmacother. 2019 Sep;117:109197. Doi: 10.1016/j.biopha.2019.109197 

Takahashi H*, Alves CRR*, Stanford KI, Middelbeek RJW, Pasquale Nigro, Ryan RE, Xue R, Sakaguchi M, Lynes MD, So K, Mul JD, Lee MY, Balan E, Pan H, Dreyfuss JM, Hirshman MF, Azhar M, Hannukainen JC, Nuutila P, Kalliokoski KK, Nielsen S, Pedersen BK, Kahn CR, Tseng YH, Goodyear LJ. TGF-β2 is an exercise-induced adipokine that regulates glucose and fatty acid metabolism. Nature Metabolism. 2019 Feb;1(2):291-303. Doi: 10.1038/s42255-018-0030-7. *co-first authorship

Souza RWA, Alves CRR, Medeiros A, Rolim N, Silva GJJ, Moreira JBN, Alves MN, Wohlwend M, Gebriel M, Hagen L, Sharma A, Koch LG, Britton SL, Slupphaug G, Wisløff U, Brum PC. Differential regulation of cysteine oxidative post-translational modifications in high and low aerobic capacity. Sci Rep. 2018 Dec 11;8(1):17772. Doi: 10.1038/s41598-018-35728-2

Alves CRR, das Neves W, Tobias GC, de Almeida NR, Barreto RF, Melo CM, Carneiro CG, Garcez AT, Faria DP, Chammas R, Brum PC. High‐intensity interval training slows down tumor progression in mice bearing Lewis lung carcinoma. JCSM Rapid Commun 2018; 1:e60, 1–10. Doi: 10.1002/j.2617-1619.2018.tb00008.x.

Alves CRR*, Faria DP, Carneiro CG, Garcez AT, Gutierrez VP, das Neves W, de Almeida NR, Cury Y, Chammas R, Brum PC*. 18F-Fluoride PET/CT and 99mTc-MDP SPECT/CT can detect bone cancer at early stage in rodents. Life Sci. 2018 Aug 1;206:29-34. Doi: 10.1016/j.lfs.2018.05.030. *co-corresponding authors

das Neves W, de Oliveira LF, da Silva RP, Alves CRR, Lancha AH Jr. Fasting: a major limitation for resistance exercise training effects in rodents. Braz J Med Biol Res. 2017 Nov 17;51(1):e5427. Doi: 10.1590/1414-431X20175427

Jannig PR, Alves CRR, Voltarelli VA, Bozi LHM, Vieira JS, Brum PC, Bechara LRG. Effects of N-acetylcysteine on isolated skeletal muscle contractile properties after an acute bout of aerobic exercise. Life Sci. 2017 Dec 15;191:46-51. Doi: 10.1016/j.lfs.2017.10.012

das Neves W, Alves CR, de Almeida NR, Guimarães FL, Ramires PR, Brum PC, Lancha AH Jr. Loss of strength capacity is associated with mortality, but resistance exercise training promotes only modest effects during cachexia progression. Life Sci. 2016 Oct 15;163:11-22. Doi: 10.1016/j.lfs.2016.08.025

Alves CR*, Borelli MT, Paineli Vde S, Azevedo Rde A, Borelli CC, Lancha Junior AH, Gualano B, Artioli GG. Development of a specific anaerobic field test for aerobic gymnastics. PloS One. 2015 Apr 13;10(4):e0123115. Doi: 10.1371/journal.pone.0123115. *corresponding author

Alves CR, da Cunha TF, da Paixão NA, Brum PC. Aerobic exercise training as therapy for cardiac and cancer cachexia. Life Sci. 2015 Mar 15;125:9-14. doi: 10.1016/j.lfs.2014.11.029

de Campos-Ferraz PL, Andrade I, das Neves W, Hangai I, Alves CR, Lancha AH Jr. An overview of amines as nutritional supplements to counteract cancer cachexia. J Cachexia Sarcopenia Muscle. 2014 Jun;5(2):105-10. doi: 10.1007/s13539-014-0138-x

Gualano B, Macedo AR, Alves CR, Roschel H, Benatti FB, Takayama L, de Sá Pinto AL, Lima FR, Pereira RM. Creatine supplementation and resistance training in vulnerable older women: a randomized double-blind placebo-controlled clinical trial. Exp Gerontol. 2014 May;53:7-15. Doi: 10.1016/j.exger.2014.02.003

Alves CR*, Tessaro VH, Teixeira LA, Murakava K, Roschel H, Gualano B, Takito MY. Influence of acute high-intensity aerobic interval exercise bout on selective attention and short-term memory tasks. Percept Mot Skills. 2014 Feb;118(1):63-72. Doi: 10.2466/22.06.PMS.118k10w4. *corresponding author

Alves CR, Merege Filho CA, Benatti FB, Brucki S, Pereira RM, de Sá Pinto AL, Lima FR, Roschel H, Gualano B. Creatine supplementation associated or not with strength training upon emotional and cognitive measures in older women: a randomized double-blind study. PloS One. 2013 Oct 3;8(10):e76301. Doi: 10.1371/journal.pone.0076301

Alves CR, Santiago BM, Lima FR, Otaduy MC, Calich AL, Tritto AC, de Sá Pinto AL, Roschel H, Leite CC, Benatti FB, Bonfá E, Gualano B. Creatine supplementation in fibromyalgia: a randomized, double-blind, placebo-controlled trial. Arthritis Care Res (Hoboken). 2013 Sep;65(9):1449-59. Doi: 10.1002/acr.22020

Alves CR,  Gualano B, Takao PP,  Avakian P, Fernandes PM, Morine D, Takito MY. Effects of acute physical exercise on executive functions: a comparison between aerobic and strength exercise. J Sport Exerc Psychol. 2012 Aug;34(4):539-49. Doi: 10.1123/jsep.34.4.539.

Alves CR, Murai IH, Ramona P, Nicastro H, Takayama L, Guimarães F, Lancha Junior AH, Irigoyen MC, Pereira RM, Gualano B. Influence of creatine supplementation on bone mass of spontaneously hypertensive rats. Rev Bras Reumatol. 2012 May-Jun;52(3):453-61.

Solis M, del Favero S, Alves CRR, Hayashi APT, Costa AS, Lugaresi R, Gualano B. Therapeutic Effects of Creatine Supplementation. In: Leon V. Berhardt. (Org.). Advances in Medicine and Biology. Volume 56. 1ed, 2012, v. 56

Alves CR, Ferreira JC, de Siqueira-Filho MA, Carvalho CR, Lancha AH Jr, Gualano B. Creatine-induced glucose uptake in type 2 diabetes: a role for AMPK-α? Amino Acids. 2012 Oct;43(4):1803-7. Doi: 10.1007/s00726-012-1246-6

Alves CR, Pasqua L, Artioli GG, Roschel H, Solis M, Tobias G, Klansener C, Bertuzzi R, Franchini E, Lancha Junior AH, Gualano B. Anthropometric, physiological, performance, and nutritional profile of the Brazil National Canoe Polo Team. J Sports Sci. 2012;30(3):305-11. Doi: 10.1080/02640414.2011.638086.

Roschel  H, Neves-Junior M, Gualano B, Barroso R, Robles C, Pinto ALS, Fuller R, Lima FR. Familiarisation with lower limb strength testing in middle-aged women with osteoarthritis of the knee. Physiotherapy. 2011 Dec;97(4):350-3. Doi: 10.1016/j.physio.2011.01.007